AL amyloidosis in a patient with IgD myeloma
Hicham Rafik1, Kawtar Hassani1, Taoufiq Aatif1, Driss El Kabbaj1, Samira E Idrissi2, Zohra Ouzzif2
1 Department of Nephrology, Mohammed V Military Hospital, Faculty of Medicine and Pharmacy, University Mohammed V-Souissi, Rabat, Morocco
2 Department of Biochemistry, Mohammed V Military Hospital, Faculty of Medicine and Pharmacy, University Mohammed V-Souissi, Rabat, Morocco
Department of Nephrology, Mohammed V Military Hospital, Faculty of Medicine and Pharmacy, University Mohammed V-Souissi, Rabat
Source of Support: None, Conflict of Interest: None
Multiple myeloma associated with IgD monoclonal protein is a well-recognized, but rare entity that affect less than 2% of patients with multiple myeloma.
Many studies including patients with IgD multiple myeloma have been published to date.,,,, This entity appears to have clinical and evolutionary differences compared with non-IgD myeloma, including a younger age at disease presentation, a higher incidence of kidney injury and a poor prognosis. A 55 years old male, with pulmonary tuberculosis in 2007, presented with lower limbs edema, dyspnea and upper limbs paresthesia for the past 4 months. He did not have bone pain. Physical examination revealed peripheral edema, macroglossia, periorbital petechial and ecchymotic lesions. There was no peripheral lymphadenopathy and no hepatosplenomegaly.
Laboratory results were as follows: serum albumin 27 g/l, total serum proteins 47 g/l, 24 hours urine protein 7 g, hematuria 3 × 104/ml, serum creatinine: 0.6 mg/dl, serum potassium: 3.7 mEq/l, serum calcium 11.3 mg/dl, hemoglobin: 11.3 g/dl, white cell count: 9.2 × 109/l and platelet count: 314 × 109/l. A renal biopsy was performed. It revealed eleven glomeruli. Three of them were sclerosed. Remaining glomeruli revealed acellular, amorphous, pale pink deposits with Congo red positivity and apple-green birefringence under polarized light. Immunofluorescence revealed that staining for lambda light chain was positive and staining for kappa light chain was negative. AL amyloidosis diagnosis was retained.
Serum protein electrophoresis showed hypogammaglobinemia 2.66 g/l that evoked free light chain myeloma [Figure 1]. Therefore, we systematically completed routine serum protein immunofixation by testing for IgD and IgE that revealed IgD lambda monoclonal immunoglobulin. Urine protein immunofixation showed lambda monoclonal free light chains at a high concentration [Figure 2]. The serum levels were IgG: 3.04 g/l, IgA: 0.18 g/l, IgM: 0.11 g/l, kappa free light chain: 0.94 mg/dl, lambda free light chain: 1218.84 mg/dl and kappa to lambda ratio <0.09. Bone marrow aspiration showed a marrow invaded by 60% of dystrophic plasma cells confirming multiple myeloma.
|Figure 2: (a) Serum protein immunofixation revealed IgD lambda monoclonal immunoglobulin. (b) Urine protein immunofixation showed lambda monoclonal free light chain|
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Standard skeletal imaging was done and was found normal. Echocardiography revealed dilated left ventricle, anterolateral hypokinesis, and good systolic function with ejection fraction at 55%. Coronary angiography showed spastic atheroma.
Due to severe cardiac involvement, (Mayo Clinic stage 4: Troponin T: 138 ng/l, N-terminal propeptide of brain natriuretic peptide: 9380 ng/l, serum free light chain difference: 12179 mg/l),, a bortezomib-cyclophosphamide-dexamethasone regimen was used for the treatment. Unfortunately, after one cycle, the patient died of myocardial infarction.
IgD amyloidosis is rare. Among 3955 patients with AL amyloidosis seen at Mayo Clinic during a period of 41 years, 53 patients (1.3%) had a serum IgD monoclonal protein. Those patients had a lower frequency of renal and cardiac involvement and had similar survival than their non-IgD counterparts.
The diagnosis of IgD amyloidosis can be difficult. In fact, the IgD monoclonal level is often small and immunofixation in search of IgD is not systematically performed. Therefore, many cases could be unnoticed or taken for a light chain myeloma.
Patients, in whom electrophoresis evoke the presence of monoclonal free light chains, should also be tested for the presence of both IgE and IgD.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Kyle RA, Gertz MA, Witzig TE, Lust JA, Lacy MQ, Dispenzieri A, et al
. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 2003;78:21-33
Jancelewicz Z, Takatsuki K, Sugai S, PruzanskiW. IgD multiple myeloma: Review of 133 cases. Arch Intern Med 1975;135:87-93.
White GC 2nd
, Jacobson RJ, Binder RA, Linke RP, Glenner GG. Immunoglobulin D myeloma and amyloidosis: Immunochemical and structural studies of Bence Jones and amyloid fibrillar proteins. Blood 1975;46:713-22.
Wechalekar A, Amato D, Chen C, Keith Stewart A, Reece D. IgD multiple myeloma: A clinical profile and outcome with chemotherapy and autologous stem cell transplantation. Ann Hematol 2005;84:115-7.
Blade J, Kyle RA. IgD monoclonal gammopathy with long-term follow-up. Br J Haematol 1994;88:395-6.
Kim MK, Suh C, Lee DH, Min CK, KIM SJ, Kim K, et al
. Immunoglobulin D multiple myeloma: Response to therapy, survival, and prognostic factors in 75 patients. Ann Oncol 2011;22:411-6.
Dispenzieri A, Gertz MA, Kyle RA, Lacy MQ, Burritt MF, Therneau TM, et al
. Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: A staging system for primary systemic amyloidosis. J Clin Oncol 2004;22:3751-7.
Kumar S, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Colby C, et al
. Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol 2012;30:989-95.
Gertz MA, Buadi FK, Hayman SR, Dingli D, Dispenzieri A, Greipp PR, et al
. Immunoglobulin D amyloidosis: A distinct entity. Blood 2012;119:44-8.
Tharp AM, Woodruff RD, Shihabi ZK. Case report: IgD-Kappa myeloma: An unusual case. Ann Clin Lab Sci 2003;33:97-100.
Pandey S, Kyle RA. Unusual myelomas: A review of IgD and IgE variants. Oncology (Williston Park) 2013;27:798-803.
[Figure 1], [Figure 2]